Which Way To An Aids Cure?

As More And More Americans Fall Victim To The Deadly Disease, The Desperate Question Grows Louder.

``where Are The Drugs To Fight It?``

September 25, 1988|By Article by Dennis L. Breo.

In 1942 Anne Miller lay hours from death from blood poisoning in Connecticut`s Yale-New Haven Medical Center. She had suffered complications from a miscarriage, and her doctors had nowhere to turn.

``We tried every known treatment, including the new sulfa drugs,`` one of her physicians, Dr. Orvan Hess, later recalled, ``but nothing could bring the fever down. She was within days of dying, and we decided to cast around for drastic new measures.``

Hess was a pioneering Yale obstetrician, and he and his colleagues decided to gamble on a last-ditch measure-a new experimental drug. The drug had been tried on only one person-in England, with inconclusive results. As Anne Miller lay in her hospital bed, the medical directors of the Allied armed forces and government officials in Washington, London and Moscow were eagerly awaiting results from the first tests of the new drug. Hundreds of scientists in a score of government and university laboratories, as well as their counterparts in three American drug companies-Merck, Pfizer and Squibb-were involved in trying to mass-produce the drug.

Through a suspenseful chain of events, Miller`s doctors persuaded U.S. government officials to release 5.5 grams of the experimental drug for their dying patient, and a messenger from Merck delivered the precious drug in a little brown bag, about a teaspoon of crystalline penicillin, about half the supply then available in the country. The drug was passed through a Seitz filter for purification and dissolved in a saline solution for intravenous injection. Penicillin was about to be tried in a human being. Miller herself was not too optimistic; she later remembered that the drug ``had the odor of mustard.``

For 14 years the drug had been in development, the product of a combination of chance and chemistry. In 1928 the British physician Alexander Fleming left an agar plate containing a culture of bacteria open to the air in the research lab of his London hospital. The spore of a rare airborne fungus happened to land on the culture and sprouted a mold that devoured the bacteria. Fleming knew that his in vitro (laboratory) observation was important, but he could not find a chemist to extract and purify the active ingredients of Penicillium notatum. About 10 years later British physicians Howard Florey and Ernest Chain devised a complicated mechanism to produce enough of the drug to prove that it destroyed disease-causing bacteria in animals (in vivo). That done, they then turned their attention to its use on humans. Nazi bombing raids, however, had by then relocated the historic quest from Oxford, England, to America.

After injecting the drug into Anne Miller, the doctors waited for a reaction. There was none. Four hours later, they gave her a larger dose. Still no reaction. They then discontinued all other medication; penicillin alone was administered. Finally, the active ingredient of penicillin homed in on the Streptococcus bacteria in Miller`s blood and collapsed their cell walls in much the same way that a pin deflates a balloon. By midnight, Miller`s temperature had fallen from 106 to 100 degrees. By morning, it was down to normal for the first time in a month. Within 24 hours, her blood, which previously had shown massive bacterial growth, was cleansed and remained so as penicillin therapy continued for the rest of her month-long convalescence.

In a 1979 interview, Anne Miller recalled, ``Even today, decades after my sickness, I am still amazed by it.``

The cost for the 60-day effort to save Miller`s life was about $1,000

(hospital room and care was $10 a day; most physician charges were canceled). ``There was no charge for the penicillin,`` Hess said wryly.

The physician added that a few months later, ``I attended a medical meeting in St. Louis where they were discussing streptococcal septicemia

(blood poisoning caused by the Streptococcus bacterium). Well, I was just a young fellow, but I arose and told them about our experience with penicillin in New Haven. They listened politely, and then the moderator said, `That`s fine, son, now you continue with your studies-and keep us informed.` He just brushed my comments aside.``

Anne Miller`s miracle, however, was not to be brushed aside. As World War II ended, another war began in earnest-the war on disease. The ``wonder drugs`` had arrived, enabling physicians to cure their patients of the various bacterial infections that had plagued mankind. Dr. Lewis Thomas, president of Memorial Sloan-Kettering Cancer Center in New York and a distinguished medical essayist, has written: ``I was a medical student at the time of penicillin, and I remember the earliest reaction of flat disbelief . . . overnight, we became optimists, enthusiasts. The realization that disease could be turned around by treatment was a totally new idea just 40 years ago.``